Kava Extract for Stress

Overseen By Jennifer Soderlind

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Mayo Clinic

Must not be taking: Kava, Acetaminophen, Steroids, others

Disqualifiers: Pregnancy, Alcohol use, Liver disease, others

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This research study is being done to assess the impact of taking Kava extract (Piper methysticum), a dietary supplement on cortisol in a healthy nursing population.

Will I have to stop taking my current medications?

The trial requires participants to stop using kava, acetaminophen, oral corticosteroids, and kratom before joining. If you use acetaminophen, you must switch to an NSAID (a different type of pain reliever) during the study.

Is kava extract safe for human use?

Kava extract is generally considered safe for short-term use at recommended doses, with most side effects being mild and reversible. However, there have been reports of serious side effects, including liver damage, so further research is needed to fully understand its safety. ^{1 2 3 4 5}

How is the drug Kava Extract for Stress different from other treatments for stress?

Kava extract, derived from the plant Piper methysticum, is unique because it contains kavalactones, which have anxiolytic (anxiety-reducing) and sedative properties. Unlike some other stress treatments, kava is a natural extract and has been traditionally used in certain cultures for its calming effects. ^{4 6 7 8 9}

Who Is on the Research Team?

Brent Bauer, MD

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

This trial is for surgical service nurses at Mayo Clinic in Rochester, MN who can fully participate and agree to use birth control during the study. It's not for those pregnant, nursing, or trying to conceive; with recent kava use; allergies to kava; heavy alcohol users; on certain medications like steroids or kratom; or with significant liver, kidney diseases, hormonal imbalances, cancer history (except specific cases), or unstable medical conditions.

Inclusion Criteria

Willing to use birth control for the duration of the study (if of childbearing potential)

I can fully participate in all parts of the study.

Surgical services nurses at Mayo Clinic in Rochester, MN

Exclusion Criteria

I am willing to use approved birth control if I have a menstrual cycle and have sex with men.

I have been diagnosed with Addison's or Cushing's Disease.

I have a known imbalance in my stress hormones or take medication that affects these levels.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Kavalactones or placebo for 28 days

4 weeks

Baseline and end of treatment visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Kavalactones
• Placebo

Trial Overview The study tests the effects of Kavalactones (found in Kava extract) versus a placebo on stress levels by measuring cortisol in healthy nurses. Participants will either receive the Kavalactones supplement or a placebo without knowing which one they are taking.

How Is the Trial Designed?

Group I: Kava Group Experimental Treatment 1 Intervention

Subjects will receive Kavalactones for 28 days

Group II: Placebo Group Placebo Group 1 Intervention

Subjects will receive placebo for 28 days

Kavalactones is already approved in United States, European Union for the following indications:

Approved in United States as Kava for:

• Anxiety
• Stress relief
• Muscle relaxation

Approved in European Union as Kava for:

• Anxiety
• Stress relief

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Published Research Related to This Trial

Kava-kava has been traditionally used for its calming effects and is now marketed for anxiety and stress relief, showing minimal negative effects on cognitive function and reaction time.

While kava-kava is generally well tolerated and non-addictive at therapeutic doses, there have been recent reports of liver toxicity in some patients, raising concerns about potential side effects, especially with high doses or prolonged use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Kava-kava and anxiety: growing knowledge about the efficacy and safety. Bilia, AR., Gallon, S., Vincieri, FF.[2019]

Kava extracts are generally well tolerated and associated with rare, mild, and reversible adverse events when used as a short-term treatment for anxiety, based on a systematic review of clinical evidence.

However, serious adverse events, including liver damage and neurological complications, have been reported, indicating the need for further research to better understand the risks associated with kava use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic review of the safety of kava extract in the treatment of anxiety. Stevinson, C., Huntley, A., Ernst, E.[2018]

The synthesized compound 6-(4-fluorophenyl)-4-methoxy-5,6-dihydropyran-2-one (2d) demonstrated strong and dose-dependent analgesic effects in various pain models, outperforming some standard reference drugs.

The analgesic action of compound 2d does not involve the opioid system and does not affect motor performance, suggesting a unique mechanism of action that warrants further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Kavain analogues as potential analgesic agents. Kormann, EC., Amaral, Pde A., David, M., et al.[2020]

A validated analytical method was developed to simultaneously quantify six major kavalactones in kava extracts, ensuring accurate quality control of these products.

Using a multi-standard approach for kavalactones resulted in significantly different content measurements compared to using only kavain as a standard, highlighting the importance of comprehensive testing for effective quality assurance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Simultaneous quantitation of kavalactones in kava dry extracts: comparison of multi-standards and single standard validation approaches. Ferreira, JV., Pierotte, IC., Pianetti, GA., et al.[2021]

The report highlights concerns about adverse events associated with concentrated standardized preparations of kava, prompting a global safety evaluation of the herb following reports from Germany and Switzerland.

It argues that many reported adverse events may not be directly linked to kava itself, suggesting that the safety issues arise more from concentrated extracts rather than traditional preparations, and proposes measures to ensure safe kava use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Kava--the unfolding story: report on a work-in-progress. Denham, A., McIntyre, M., Whitehouse, J.[2019]

The Kava Anxiety Depression Spectrum Study (KADSS) is the first clinical trial to assess the effectiveness of an aqueous extract of kava for treating anxiety and depression, involving 60 adult participants over a 3-week period.

If the study finds that kava is both effective and safe, it could lead to its re-introduction in Europe, the UK, and Canada, benefiting both individuals with anxiety disorders and the economies of Pacific Island nations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Kava Anxiety Depression Spectrum Study (KADSS): a mixed methods RCT using an aqueous extract of Piper methysticum. Sarris, J., Kavanagh, DJ., Adams, J., et al.[2009]

Piper methysticum extract (kava kava) and its principal component, dihydrokavain, were found to reduce distress vocalizations in chicks subjected to social separation stress, indicating potential anxiolytic effects.

The study involved eight-day-old chicks receiving various treatments, showing that both kava extract and dihydrokavain can alleviate anxiety-like behaviors, suggesting their therapeutic potential for anxiety management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anxiolytic effects of kava extract and kavalactones in the chick social separation-stress paradigm. Smith, KK., Dharmaratne, HR., Feltenstein, MW., et al.[2019]

A study on Wistar rats, which were given ethanolic kava extract for 3 to 6 months, showed no signs of chronic toxicity, including no adverse effects on body weight or liver health.

These findings support the traditional use of kava preparations in the South Pacific and suggest that concerns about liver toxicity may be unfounded.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of ethanolic kava extract: Results of a study of chronic toxicity in rats. Sorrentino, L., Capasso, A., Schmidt, M.[2010]

Kava extract demonstrated anxiolytic effects and reduced stereotyped behaviors induced by amphetamine in mice, suggesting its potential to alleviate psychotic symptoms.

The study found that Kava extract decreased the activity of monoamine oxidase (MAO) enzymes in specific brain regions, which may contribute to its therapeutic effects in managing anxiety and psychosis-like symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Kava decreases the stereotyped behavior induced by amphetamine in mice. Krum, BN., Molz de Freitas, C., Chiapinotto Ceretta, AP., et al.[2021]

Citations

1. Netherlands pubmed.ncbi.nlm.nih.gov

Kava-kava and anxiety: growing knowledge about the efficacy and safety. [2019]

2. New Zealand pubmed.ncbi.nlm.nih.gov

A systematic review of the safety of kava extract in the treatment of anxiety. [2018]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Kavain analogues as potential analgesic agents. [2020]

4. England pubmed.ncbi.nlm.nih.gov

Simultaneous quantitation of kavalactones in kava dry extracts: comparison of multi-standards and single standard validation approaches. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Kava--the unfolding story: report on a work-in-progress. [2019]

6. Scotland pubmed.ncbi.nlm.nih.gov

Kava Anxiety Depression Spectrum Study (KADSS): a mixed methods RCT using an aqueous extract of Piper methysticum. [2009]

7. Germany pubmed.ncbi.nlm.nih.gov

Anxiolytic effects of kava extract and kavalactones in the chick social separation-stress paradigm. [2019]

8. Germany pubmed.ncbi.nlm.nih.gov

Safety of ethanolic kava extract: Results of a study of chronic toxicity in rats. [2010]

9. Ireland pubmed.ncbi.nlm.nih.gov

Kava decreases the stereotyped behavior induced by amphetamine in mice. [2021]